The long-term goals of the proposed research are to demonstrate the cariostatic properties and biocompatibility of a previously developed Ca-PO4 Resin Cement (CP-RC) and to investigate the in vitro and in vivo properties of a novel Ca- PO4-enriched Bonding Agent (CP-BA). Both CP-RC and CP-BA are based on acidic- and other dimethacrylate resins, Ca-PO4 fillers and fluoride additives. The cement will provide the handling characteristics necessary for its clinical use as a direct or indirect pulp-capping agent. It has high pH during and after setting, moderate fluoride release, and has been shown in vitro to remineralize artificial tooth lesions. However, while the cement has shown moderate adhesive properties, its bond strength to dentin is low compared to those of current bonding agents. Moreover, preliminary tests showed that bonding agents placed between CP-RC and dentin with artificial caries-like lesions significantly reduced their remineralization. Thus, there is a need to explore novel dentin bonding agents with remineralizing/cariostatic properties and strong adhesion to normal and mineral-deficient dentin. Such adhesives could serve as conventional restorative bonding agents and for pulp-capping purposes. The specific aims are to 1. evaluate CP-RC effectiveness for preventing secondary caries formation in adjacent dentin and enamel; 2. (i) analyze qualitatively and quantitatively leachable components from the cement; and (ii) determine the in vitro cytotoxicity and effects on odontoblast cell culture and compare the in vitro biocompatibility and cytodifferentiation of CP-RC with the results from an (ongoing) in vivo animal study on the pulp-capping efficacy of the cement; 3. investigate bonding systems containing the same adhesive resin and Ca-PO4 fillers as the CP-RC and characterize their bioactivity effects and reinforcing mechanisms 4. evaluate the biocompatibility and cytodifferentiation of an optimized CP-BA and 5. address the controversial question of whether adhesive bonding agents can be successfully applied to pulp-capping procedures by evaluating the in vivo pulp-capping efficacy of this novel biocompatible, bioactive bonding agent. Completion of this research will lead to a remineralizing pulp-capping/lining cement and a bioactive Ca-PO4 dentin adhesive The CaPO4 resin cement will provide a method to reliably treat mechanical and small carious pulp exposures by stimulating the natural formation of dentin bridging with a base that has moderate adhesion to prevent leakage and the strength to allow the immediate placement of a permanent restoration. A remineralizing adhesive will provide methods of adhering to mineral-deficient dentin and for covering exposed pulps. The proposed studies will also provide a valuable comparison of in vivo test results to pulp cell response in vitro.